Project abstract Funds are requested to support the 2009 Proteins Gordon Research Conference. This is a long-standing and usually oversubscribed meeting that serves the scientific community and is focused on the fundamental properties of protein molecules, including their structure, folding, dynamics, stability, and interactions. As vice chairs of the 2007 meeting, Fetrow and Oas participated in a conscious decision on the part of chairs Hill and Pielak to incorporate a more cellular focus in the session and talk topics. This updating of Proteins was generally well received by the participants of the 2007 meeting and we have developed a program that continues in this vein. However, we have also recognized that the participation of the scientists who laid the foundation for modern protein science was lower in 2007 than in previous years. To increase their participation, we have developed a program designed to provide younger protein scientists with the insights and perspectives accomplished senior leaders of the field can provide. These senior scientists will chair sessions whose topics their work has significantly impacted. They will present talks at the beginning or end of their session, which will provide historical context to exciting new sub-fields of protein science and lead the 30-minute discussions at the end of each session. Speakers in each session include younger scientists, whose work focuses on proteins in their biological context. In this way, we will bring together the best of classical protein science with the best of the newer research in the field. In choosing topics and speakers for the 2009 meeting, we sought input from the protein science community and have incorporated suggestions offered in response to the 2007 program. The current co-vice chairs, Clark and Bowie, are also heavily involved in planning the 2009 meeting. In response to a criticism of the 2007 meeting, we are planning several measures to increase the interaction between all meeting participants, particularly the senior and junior scientists. In addition to a final keynote session, the 2009 schedule includes the following regular sessions: 1. Post-reductionist protein science;2. Role of co-solutes and water in protein stability;3. Protein-RNA biology;4. The hydrogen bond and hydrophobicity, revisited;5. Theory of amyloid formation;6. Functional consequences of protein heterogeneity;7. Protein function and ligand binding in the cell. Public Health Relevance: Project narrative, including health-related significance Proteins are central actors in most biological processes, including those relevant to human health. Proteins are involved in such important biological processes as signaling pathways, metabolism, and gene expression. They are the usual targets of therapeutic drugs and protein mutation, mis-folding or dysfunction is directly implicated in many diseases. The 2009 Proteins GRC will explore recent advances and future trends in understanding the structure, stability, motions, and interactions of protein molecules and how these fundamental properties impact function in the biological context.